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This study aimed to evaluate the anti\u2010HCC potential of the petroleum ether extract of\n                    <jats:italic>Ficus pandurata<\/jats:italic>\n                    Hance (FPHPE), a traditional hepatoprotective herb, focusing on its pro\u2010apoptotic and anti\u2010inflammatory actions via the JAK2\/STAT3 signaling pathway. In\u00a0vitro experiments demonstrated significant growth inhibition of HepG2, SMMC7721, and Hep3B cells following FPHPE treatment. GC\u2013MS profiling identified 26 phytoconstituents, including friedelane, seseline, bergaptan, and tocopherols, many with known bioactivity. In a xenograft mouse model, FPHPE markedly suppressed tumor growth without causing systemic toxicity. Mechanistic analyses demonstrated that FPHPE activated mitochondria\u2010mediated apoptosis, as confirmed by Annexin V\/PI flow cytometry, Western blot quantification from three biological replicates, TEM imaging showing disrupted cristae, and JC\u20101 staining revealing mitochondrial membrane depolarization. Concurrently, FPHPE downregulated phosphorylated and total JAK2\/STAT3, inhibited STAT3 nuclear translocation, and suppressed key downstream effectors (iNOS, COX2, c\u2010Myc, Vimentin, and Slug). ELISA further confirmed a reduction of pro\u2010inflammatory cytokines TNF\u2010\u03b1 and IL\u20101\u03b2 in tumor tissues. Together, these findings establish FPHPE as a dual\u2010action phytotherapeutic candidate that interrupts both survival and inflammatory pathways, positioning\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>F. pandurata<\/jats:italic>\n                    <\/jats:styled-content>\n                    as a promising source for nutraceuticals or complementary therapies against inflammation\u2010driven liver cancer.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71114","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T04:36:38Z","timestamp":1762317398000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Ficus pandurata<\/i>\n                    as a Functional Phytotherapeutic: Inhibiting\n                    <scp>JAK2<\/scp>\n                    \/\n                    <scp>STAT3<\/scp>\n                    Signaling and Activating Mitochondrial Apoptosis in Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Muhammad","family":"Majid","sequence":"first","affiliation":[{"name":"Dongguan Key Laboratory of Fundamental Research and Clinical Application of Toxic Chinese Medicine The First Dongguan Affiliated Hospital, Guangdong Medical University  Dongguan P.R. 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